Many hormones and neurotransmitters regulate functions in a living body through specific receptor proteins existing in a cell membrane. Many of these receptor proteins mediate signal transmission in a cell by activation of coupled guanine nucleotide-binding proteins (hereinafter, sometimes, referred to as G-proteins) and are generally called G-protein coupled receptor proteins or 7-transmembrane receptor proteins because they contain a common structure having seven transmembrane domains.
G-protein coupled receptor proteins exist on each functional cell surface of cells and internal organs of a living body and play very important roles as targets of molecules which regulate functions of the cells and internal organs of the living body, for example, hormones, neurotransmitters, physiologically active substances and the like.
To clarify the relation between substances which regulate elaborate functions in cells and internal organs of various living bodies and their specific receptor proteins, in particular, G-protein coupled receptor proteins provide a very important means for clarification of functional mechanisms of cells and internal organs of various living body as well as for development of drugs having close relation to such functional mechanisms. For example, in a central nerve system organ such as a brain, its physiological functions are controlled through regulation by many hormones, hormone-like substances, neurotransmitters, physiologically active substances or the like. In particular, neurotransmitters are found in numerous sites within a brain and regulate the physiological functions thought their corresponding receptor proteins.
However, it is supposed that many unknown neurotransmitters still exist in a brain and, as for their receptor proteins, many structures of cDNAs encoding such proteins have not yet been reported. In addition, it is still unknown if there are subtypes of known receptor proteins.
Also, to clarify the relation between substances which regulate elaborate functions in a brain and their specific receptor proteins provides a very important means for development of drugs. Further, for screening for agonists and antagonists to receptor proteins, efficiently, in development of drugs, it is required to clarify functional mechanisms of receptor protein genes expressed in a brain and to express them in a suitable expression system.
Recently, as a means for analyzing genes expressed in a living body, random analysis of cDNA sequences has been studied actively. The sequences of cDNA fragments thus obtained have been registered with data bases as Expressed Sequence Tags (ESTs) and are publicly available. However, for many of ESTs, it is difficult to deduce their functions from their sequential information only. For example, although two ESTs, accession No. T08099 (SEQ ID NO: 5) and No. T27053 (SEQ ID NO: 6), have been registered with the data base, NCBI dbEST, their functions are not clarified.